Amyloid-β-induced ion flux in artificial lipid bilayers and neuronal cells: Resolving a controversy

Abstract

Understanding the pathogenicity of amyloid-beta (Aβ) peptides constitutes a major goal in research on Alzheimer's disease (AD). One hypothesis entails that Aβ peptides induce uncontrolled, neurotoxic ion flux through cellular membranes. The exact biophysical mechanism of this ion flux is, however, a subject of an ongoing controversy which has attenuated progress toward understanding the importance of Aβ-induced ion flux in AD. The work presented here addresses two prevalent controversies regarding the nature of transmembrane ion flux induced by Aβ peptides. First, the results clarify that Aβ can induce stepwise ion flux across planar lipid bilayers as opposed to a gradual increase in transmembrane current; they show that the previously reported gradual thinning of membranes with concomitant increase in transmembrane current arises from residues of the solvent hexafluoroisopropanol, which is commonly used for the preparation of amyloid samples. Second, the results provide additional evidence suggesting that Aβ peptides can induce ion channel-like ion flux in cellular membranes that is independent from the postulated ability of Aβ to modulate intrinsic cellular ion channels or transporter proteins.